INOTROPES not easy,so heres a lil bit of a background to hopefully help understand how they work for those who already k

1. INOTROPES =not easy,so heres a lil' bit of a background to hopefully help understand how they work for those who already know this please bear with it, for those who like me need things simply hope it helps! Acute care: Circulatory failure and use of inotropes blood pressure (BP) is the product of cardiac output (CO) and systemic vascular resistance (SVR)--that is, BP=CO*SVR. Therefore a low blood pressure can be due to a low cardiac output (low flow) or reduced systemic vascular resistance (vasodilatation) or both. Pressure and flow are not the same thing. There is no "normal" blood pressure. What matters is whether a low blood pressure is causing a problem.

2. Cardiac output Cardiac output depends on the interrelated factors of heart rate (HR) and stroke volume (SV)--that is, CO=HR*SV. Stroke volume, is the volume of blood ejected in a single ventricular contraction. This, in turn, depends on three things--contractility, preload, and afterload. Contractility is the amount of mechanical work done for a given preload and afterload. It is increased by sympathetic stimulation and inotropes. It is reduced by parasympathetic stimulation, negative inotropes http://www.studentbmj.com/issues/04/05/education/190.php

3. Inotropes An INOTROPE is an agent which increases or decreases the force or energy of muscular contractions. Negatively Inotropic agents weaken the force of muscular contractions. Positively Inotropic agents increase the strength of muscular contraction.

4. Inotropes Inotropes are non-habit-forming medications that strengthen the contractions of the heart so the heart can pump more blood with fewer beats. Certain inotropes may be prescribed to slow the heart rate of people with an abnormally fast heart rhythm (tachycardia). or to strengthen the pumping ability of a heart that is weakened�because of heart failure. (Elhendy et al,2007) http://heart.health.ivillage.com/inotropes/cardiotonics.cfm

5.  Inotropes work via the automatic immune system sorry those who already know this bit! 1. THE AUTONOMIC NERVOUS SYSTEM REGULATES ACTIVITIES THAT ARE AUTOMATIC, OR INVOLUNTARY. 2. The Nerves of the Autonomic Nervous System CONTROL Functions of the body that are NOT UNDER CONSCIOUS CONTROL. 3. The Autonomic Nervous system seems to be concerned with striking a balance or MAINTAINING HOMEOSTASIS IN THE FUNCTIONING OF MANY ORGANS OF THE BODY. EXAMPLES:� CONTRACTION IN THE HEART, DIGESTION, HEART RATE, BREATHING, SALIVATION, AND BLADDER. ���

6. Bit of revision (�,) THE AUTONOMIC NERVOUS SYSTEM IS FURTHER SUBDIVIDED INTO TWO PARTS: ��� A. THE SYMPATHETIC DIVISION ��� B. THE PARASYMPATHETIC DIVISION The TWO parts have OPPOSITE EFFECTS on the ORGANS they control. Most organs controlled by the Autonomic Division are under control of both Sympathetic and Parasympathetic Neurons. EXAMPLE:�� Heart Rate is SPEEDED UP by the Sympathetic Nervous System, and it is SLOWED DOWN by the Parasympathetic Nervous System. The Sympathetic Division generally ACTIVATES ORGANS or SPEEDS UP. The Parasympathetic Division generally RETARDS ORGANS or SLOWS DOWN.

7. Autonomic Nervous System

8. Getting back��HOW DO INOTROPES WORK? Inotropes act directly or indirectly on the Sympathetic Nervous System, but the effect of each varies according to which sympathetic receptor the drug has greatest affinity for. The duration of action also varies. Direct acting drugs act by stimulating the SNS receptor whereas indirect acting drugs cause the release of noradrenaline from the receptor which produces the effect. Some drugs have a mixed effect http://www.nda.ox.ac.uk/wfsa/html/u10/u1004_01.htm

9. Sympathetic Nervous System Originates in the spinal cord 1st synapse in sympathetic chain ACH as neurotransmitter in Sympathetic chain Noradrenaline in target organ. Adrenaline release from the adrenal medulla Thanks Diane for this slide!

10. Parasympathetic Nervous System PNS acetylcholine is the neurotransmitter. Sympathetic Nervous System (SNS) are noradrenergic receptors and noradrenaline is the neurotransmitter. Noradrenalin is the primary neurotransmitter released by the sympathetic nervous system, which mediates the �fight or flight� reaction, preparing the body for action by affecting cardiovascular function, gastrointestinal motility and secretion, bronchiole dilation, glucose metabolism, and so on. These noradrenergic receptors are further subdivided, Alpha1 (a1), Beta1 (b1), Beta2 (b2) and Dopamine (D).

11. So When you Stimulate the Sympathetic Nervous System What happens? Depends on what you stimulate it with but�. Noradrenaline and Adrenaline levels go up This causes activation of adrenergic receptors located in the ENDOTHELIUM

12. The endothelium The endothelium compromoses a layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. Endothelium of the interior surfaces of the heart chambers are termed as endocardium. Both blood and lymphatic capillaries are composed of a single layer of endothelial cells

13. Endothelial cells are involved in many aspects of vascular biology, including: vasoconstriction and vasodilation, and hence the control of blood pressure blood clotting (thrombosis & fibrinolysis) atherosclerosis formation of new blood vessels inflammation and swelling (oedema) Endothelial cells also control the passage of materials � and the transit of white blood cells � into and out of the bloodstream.

14. How do they work? Two types of Adrenergic receptors 9 in total Both found in the vascular endothelium Alpha (a) 1 & 2 Vascular smooth muscle and urinary tract Beta (�) 1 & 2 Heart (�1)

16. Alpha Receptors Cardiac alpha 1 Stimulation causes increase in contractility without an increase in rate. Alpha 1 and alpha 2 In peripheral vessels mediate vasoconstriction

17. Beta Receptors Beta 1 STIMULATION causes increased rate and force of cardiac contraction Beta 2 receptors = Bronchial smooth muscle dilation. Vasodilation in skeletal muscle. Also some cardiac effects

18. Dopamine Receptors Stimulation = increased renal and coronary blood flow Arterial vasodilatation

19. Inotropic Drugs POSITIVE Cardiac contractibility Digoxin Adrenaline and Noradrenalin Dobutamine Dopamine Isoprenaline NEGATIVE cardiac contractibility Beta blockers Calcium channel blockers

20. Risks and Benefits of Inotropes BENEFITS Improves cardiac performance Improves contractility of myocardium Increase blood pressure RISK Increased heart rate causing further deterioration of failing heart pump Increases myocardial oxygen requirements Potentially arrythmogenic Can increase ischaemia

21. ADRENALINE Adrenaline acts on a1, b1 and b2 receptors. It is said to prepare the body for a "fight or flight" response. Actions CVS: Increased heart rate and force of contraction produce an increase in cardiac output. Systolic blood pressure (SBP) rises, but with low doses diastolic blood pressure (DBP) may fall due to vasodilation and increased blood flow through skeletal muscle beds (b2). At higher doses the vasoconstrictor effects of a1 stimulation become more apparent, causing the cool pale extremities of a frightened person. RS: Bronchial smooth muscle is relaxed resulting in bronchodilation (b2). Other: Adrenaline mobilises glucose from glycogen and raises blood sugar. Pupillary dilation (mydriasis) occurs. Side effects Ventricular arrhythmias, hypertension. Care with halothane anaesthesia as arrhythmias may occur. Acute severe asthma attack unresponsive to normal treatment may require infusions of adrenaline, Septic shock - require infusions of adrenaline Length of action Short, few minutes only with intravenous bolus

22. Inotropes given by infusion The inotropes listed below are only given by infusion unless a bolus dose is stated. They are mostly very short acting, their effects lasting from a few seconds to one or two minutes and should be given via a central line. The patient must be closely monitored, particularly the ECG and blood pressure. Tachycardia, arrhythmias, and hypertension or hypotension are side effects of these drugs. Although called inotropes some of these drugs also have vasoconstrictor properties. Noradrenaline Dopamine Dobutamine Isoprenaline

23. DOBUTAMINE Mainly beta 1 effects increased rate and force of cardiac contraction Tolerance may be seen after 48-72 hrs, may necessitate an increase in dose Acts on b1 and b2, with minimal action on a1 receptors. Actions It increases cardiac output and reduces afterload (b2effects on skeletal muscle). Indications Cardiogenic shock.

24. Dopamine Acts on D, b1, b2 and a1 receptors, depending on the dose administered. Actions Dose dependent. It used to be popular to increase urine output via its effect on the D receptors in the kidney. However, less commonly used for this purpose as it does not prevent renal failure. Indications Hypotension. Dose 1-2mcg/kg/min - acts on D receptors usually increasing urine output 2-10mcg/kg/min - also acts on b receptors to increase cardiac output

25. Isoprenaline Acts on b1 and b2 receptors Only used as part of an emergency management of complete heart block Powerful vasodilator effects �can cause undesirable fall in blood pressure Give oxygen Increase rate of infusion slowly and observe for adverse side effects

26. Administration Supremely dangerous Miniscule doses calculated on body weight Titrated infusion (except adrenaline in cardiac arrest) Close monitoring (ECG & Arterial line) Piggy Back ? Side effects

27. Inotrope infusions are a stop gap measure The underlying cause must be treated or symptoms controlled Managing infusions Don�t let infusions run out � make up infusions with time to spare Change over infusions with new lines as quickly as possible